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. 2025 Apr 10;24(1):136.
doi: 10.1186/s12944-025-02541-6.

Central adiposity and α-klotho: inflammatory mechanisms underlying aging biomarkers related to body roundness index

Rui Du #  1 , Xiaoyan Tang #  2 , Lei Guan  2 , Yuchen Lai  3 , Huijuan Xiang  4 , Wei Huang  5
Affiliations

Central adiposity and α-klotho: inflammatory mechanisms underlying aging biomarkers related to body roundness index

Rui Du et al. Lipids Health Dis. .

Abstract

Background: Obesity is a global health issue which has been widely accepted as an aging related pathogenesis. α-Klotho is a protein involved in aging process, mineral metabolism, insulin sensitivity, and the pathogenesis of various age-related diseases. Adiposity correlates with lower soluble α-Klotho, but the role of fat distribution and inflammation remains unclear. The body roundness index (BRI) refines central adiposity assessment beyond BMI. Herein, We aimed to investigate the relationship of BRI, inflammation and serum level of soluble α-Klotho.

Methods: We conducted a cross-sectional analysis of 9,958 U.S. adults (40-79 years) from the 2007-2016 NHANES. We examined association between BRI and serum α-Klotho (SαKl) levels, controlling for demographic, socioeconomic, lifestyle, and clinical factors. We also assessed whether inflammatory markers mediated the BRI-SαKl relationship.

Results: BRI was inversely associated with SαKl levels (P < 0.05). A significant sex interaction was found (P < 0.001), while BRI was positively correlated with multiple proinflammatory markers, which were all inversely related to SαKl levels. Mediation analyses showed inflammatory markers accounted for 20.5% (WBC), 18.0% (neutrophils), and 12.3% (platelets) of the BRI-SαKl association.

Conclusion: More severe central adiposity measured by BRI was related to lower SαKl, which may partly be attributed to inflammation. These findings underscore the importance of fat distribution and inflammation in obesity-related aging and may guide interventions to preserve SαKl levels. Longitudinal studies are needed to confirm causality and inform future strategies.

Keywords: Aging; Body roundness index; NHANES; Obesity; α−Klotho.

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Conflict of interest statement

Declarations. Ethics approval and consent to participate: The survey was administered by the National Center for Health Statistics (NCHS) and approved by the NCHS Institutional Review Board (IRB). Informed consent was obtained from the eligible subjects before initiating the data collection and NHANES health examinations. All the authors confirmed that all the methods were carried out in accordance with the relevant NHANES Analytic Guidelines. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Subgroup analyses of the association between BRI and serum α−Klotho levels Each stratification adjusted for all factors (age, gender, race/ethnicity, marital status, PIR, education level, smoking status, alcohol consumption status, physical activity, diabetes, hypertension, CKD, and CVD) except the stratification factor itself. Abbreviations: PIR, Poverty income ratio; CKD, chronic kidney disease; CVD, cardiovascular disease
Fig. 2
Fig. 2
Mediation model of the effect of BRI and serum α−Klotho levels Abbreviations: BRI, Body Roundness Index; CI, Confidence interval; WBC: White blood cell
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